Description (Applicant Abstract): The fundamental changes in the human cardiovascular system that occur with age are of importance in physiology, pathophysiology, and clinical medicine. Clearly, the diagnosis and management of cardiovascular disease in the rapidly growing USA senescent population is complicated by normal age-related differences in the cardiovascular system. During the first three years of our NIH/MBRS support, we have uniquely provided a comprehensive study on age-related differences in human regional blood flows and distributions of cardiac output under important, daily physical stresses. Data was obtained from cohorts 20-30 and 70-80 years old. Presently, no important data are available from an elderly group, 80-90 years old, and, by contrast, the developing years of 10-20 years. Accordingly, we well test the hypothesis that there are significant age-related differences in steady-state and transient human regional blood flows, and percentages of cardiac output in the 80-90 and 10-20 year old cohorts. Our specific aims are to noninvasively measure Doppler blood velocity spectral waveforms and systolic lumen diameters in major conduit arteries. Data will be obtained from the following arteries which supply the majority of blood to specific organ systems shown parenthetically: 1) common carotid (cerebral); 2) subclavian (upper limb); 3) superior mesenteric (splanchnic); 4) renal (kidney); and 5) common femoral (lower limb). With the simultaneous measurements of cardiac output and phasic tonometric blood pressures, the time courses of regional blood flows and arterial input impedances will be determined. By power analysis, 60 subjects (30 male, 30 female) from two separate age groups (10-19, and 80-89 years) will be exposed to the following common stresses: 1) orthostatic tilt (postural changes); 2) hypoxia (increased altitude or respiratory dysfunction); 3) postprandial (meals or oral medication); and 4) graded exercise (physical exercise). Criteria for inclusion in the study will be a normal body size, clinical history, physical examination, exercise stress test, laboratory studies, and echogenic, nonstenotic arteries. Analysis of covariance will determine significant age-related differences in both the absolute values and percentage changes of regional blood flows, impedances, and percentages of cardiac output. This obvious extension of our ongoing study will provide direct noninvasive data on age-related differences in the reactivity and volume of normal human regional blood flows and thus mass transport in arteries which 1) supply major organ systems; 2) are susceptible to obstructive lesions whose significance depends on flow rates and arterial input impedances; and 3) are appropriate for noninvasive diagnosis and therapeutic interventions.